The increased activity in cancer cells of inosine 5'-monophosphate dehydrogenase (IMPD) or inosinic acid dehydrogenases in general has led to the suggestion that inosinic acid dehydrogenases be used as a sensitive target for chemotherapy. Inosine 5'-monophosphate dehydrogenase is the rate-limiting enzyme of de novo guanosine 5'-triphosphate (GTP) biosynthesis, with GPT playing a key role in polypeptide chain activation during protein synthesis and other vital anabolic biochemical processes. Various inhibitors of IMPD have been used as cancer chemotherapeutic treatments, therefore, including tiazofurin (NSC 286193, 2-beta-D-ribofuranosylthiazole-4-carboxamide) and mycophenolic acid. In some clinical trials, tiazofurin (through its metabolic conversion to the active metabolite thiazole-4-carboxamide adenine dinucleotide (TAD)) caused return to a chronic phase in patients with chronic granulocytic leukemia in blast crisis. Mycophenolic acid and retinoic acid have been documented as inducing maturation of malignant cells. Tiazofurin was found to be a highly effective inhibiting agent of solid tumor metastasis in mice. Other efforts are ongoing in the investigation of the efficacy of IMPD inhibitors in the treatment of various tumors, and these efforts are generally regarded as effective and/or promising.
To the extent that IMPD-inhibitors continue to be indicated and prescribed to combat neoplasms exhibiting elevated IMPD levels, health care providers have need of a reliable and relatively simple diagnostic assay for IMPD. Previous assays for IMPD have primarily if not exclusively involved biochemical analysis of tissue homogenates, but such assays have serious drawbacks. For one thing, in a given tumor biopsy both tumor cells and nontumor cells (lymphocytes, for example, and other immune and non-immune cells) are present. An assay of a homogenate of these tumor and nontumor cells will not indicate the IMPD level in the tumor cells alone but in the homogenate as a whole--even though it is an elevated IMPD level in the actual tumor cell which is predictive of successful IMPD-inhibitor treatment. A need therefore remains for an IMPD assay which can quantify IMPD within individual tumors or otherwise morphologically classified animal or human cells.